PURPOSEA previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.METHODSA total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (%0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).RESULTSThe high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P <.0001), CIR (59.7% v 35.2%; P <.0001), and OS (49.2% v 70.5%; P <.0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P <.0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P <.0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P =.016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P =.00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.CONCLUSIONEOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
Van Weelderen, R. E., Klein, K., Harrison, C. J., Jiang, Y., Abrahamsson, J., Arad-Cohen, N., Bart-Delabesse, E., Buldini, B., De Moerloose, B., Dworzak, M. N., Elitzur, S., Fernandez Navarro, J. M., Gerbing, R. B., Goemans, B. F., De Groot-Kruseman, H. A., Guest, E., Ha, S. -., Hasle, H., Kelaidi, C., Lapillonne, H., Leverger, G., Locatelli, F., Masetti, R., Miyamura, T., Noren-Nystrom, U., Polychronopoulou, S., Rasche, M., Rubnitz, J. E., Stary, J., Tierens, A., Tomizawa, D., Zwaan, C. M., Kaspers, G. J. L., Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A -Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group, <<JOURNAL OF CLINICAL ONCOLOGY>>, 2023; 41 (16): 2963-2974. [doi:10.1200/JCO.22.02120] [https://hdl.handle.net/10807/276679]
Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A -Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group
Locatelli, Franco;
2023
Abstract
PURPOSEA previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.METHODSA total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (%0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).RESULTSThe high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P <.0001), CIR (59.7% v 35.2%; P <.0001), and OS (49.2% v 70.5%; P <.0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P <.0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P <.0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P =.016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P =.00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.CONCLUSIONEOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
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